OpenLB
Open Library of Bioscience
Advanced Search
Journal of leukocyte biology
02, 2019;105 (2): 267-280.

The pathogenesis of tuberculous meningitis.

Angharad Grace Davis, Ursula Karin Rohlwink, Alizé Proust, Anthony A Figaji, Robert J Wilkinson
Author Information
  1. Angharad Grace Davis: The Francis Crick Institute, Midland Road, London, United Kingdom.
  2. Ursula Karin Rohlwink: Neuroscience Institute, Division of Neurosurgery, University of Cape Town, Republic of South Africa.
  3. Alizé Proust: The Francis Crick Institute, Midland Road, London, United Kingdom.
  4. Anthony A Figaji: Neuroscience Institute, Division of Neurosurgery, University of Cape Town, Republic of South Africa.
  5. Robert J Wilkinson: The Francis Crick Institute, Midland Road, London, United Kingdom.
PMID: 30645042 DOI: 10.1002/JLB.MR0318-102R

Abstract

Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury. Here we review the steps from primary infection to cerebral disease, factors that contribute to the virulence of the organism and the vulnerability of the host and discuss the immune response and the clinical manifestations arising. Priorities for future research directions are suggested.

Keywords

Th17 cells T Lymphocytes endothelial cells granulocytes microglia cells monocytes/macrophages mycobacterial myeloid cells neutrophils

References

  1. Emerg Infect Dis. 2001 Sep-Oct;7(5):880-3 [PMID: 11747703]
  2. J Infect Dis. 2017 Mar 1;215(5):677-686 [PMID: 27932622]
  3. Int J Tuberc Lung Dis. 2003 Dec;7(12):1186-90 [PMID: 14677894]
  4. Tuberculosis (Edinb). 2014 Dec;94(6):657-63 [PMID: 25257262]
  5. Clin Infect Dis. 2017 Oct 15;65(8):1298-1307 [PMID: 28605426]
  6. Pediatr Infect Dis J. 2004 Jul;23(7):608-13 [PMID: 15247597]
  7. Springerplus. 2016 Oct 12;5(1):1775 [PMID: 27795917]
  8. J Neurovirol. 2005 Jul;11(3):265-73 [PMID: 16036806]
  9. J Clin Invest. 1998 Jan 15;101(2):311-20 [PMID: 9435302]
  10. Clin Vaccine Immunol. 2010 Jul;17(7):1094-103 [PMID: 20463103]
  11. Nat Genet. 2013 Oct;45(10):1176-82 [PMID: 23995134]
  12. J Clin Microbiol. 2007 Feb;45(2):409-14 [PMID: 17166963]
  13. J Infect. 2009 Sep;59(3):156-66 [PMID: 19635500]
  14. N Engl J Med. 2004 Oct 21;351(17):1741-51 [PMID: 15496623]
  15. Ann Clin Lab Sci. 2017 Sep;47(5):628-637 [PMID: 29066494]
  16. PLoS One. 2012;7(7):e40221 [PMID: 22844400]
  17. J Neurol Sci. 2016 Aug 15;367:152-7 [PMID: 27423581]
  18. Ann Indian Acad Neurol. 2014 Apr;17(2):171-8 [PMID: 25024567]
  19. PLoS One. 2012;7(8):e43170 [PMID: 22916219]
  20. Front Biosci. 2002 May 01;7:d1356-68 [PMID: 11991838]
  21. J Infect Dis. 1996 May;173(5):1194-201 [PMID: 8627072]
  22. PLoS Med. 2010 Dec 21;7(12):e1000384 [PMID: 21253011]
  23. J Infect Dis. 2017 Apr 1;215(7):1020-1028 [PMID: 28419368]
  24. PLoS Pathog. 2008 Mar 28;4(3):e1000034 [PMID: 18369480]
  25. Annu Rev Immunol. 2013;31:475-527 [PMID: 23516984]
  26. Eur Respir J. 2011 May;37(5):1248-59 [PMID: 20817712]
  27. J Neurosci. 2009 Apr 1;29(13):4200-9 [PMID: 19339614]
  28. Tuberculosis (Edinb). 2015 Mar;95(2):190-6 [PMID: 25616954]
  29. Clin Infect Dis. 2013 Feb;56(3):450-60 [PMID: 23097584]
  30. J Neuroinflammation. 2007 Nov 26;4:27 [PMID: 18036262]
  31. PLoS Pathog. 2011 Mar;7(3):e1001307 [PMID: 21408618]
  32. Elife. 2015 Mar 03;4: [PMID: 25732036]
  33. J Immunol. 2006 Feb 1;176(3):2007-14 [PMID: 16424233]
  34. FEMS Immunol Med Microbiol. 2000 Sep;29(1):27-33 [PMID: 10967257]
  35. J Korean Neurosurg Soc. 2013 Jul;54(1):61-4 [PMID: 24044085]
  36. Pediatr Res. 1999 Apr;45(4 Pt 1):459-64 [PMID: 10203135]
  37. J Clin Microbiol. 2006 Nov;44(11):3934-9 [PMID: 16971650]
  38. Infection. 2003 Mar;31(2):115-7 [PMID: 12682818]
  39. Neurol Med Chir (Tokyo). 2012;52(10):761-4 [PMID: 23095273]
  40. Genes Immun. 2007 Jul;8(5):422-8 [PMID: 17554342]
  41. Cell. 2012 Feb 3;148(3):434-46 [PMID: 22304914]
  42. Front Physiol. 2014 Jul 02;5:244 [PMID: 25071589]
  43. Pediatr Infect Dis J. 2015 Feb;34(2):214-8 [PMID: 25741973]
  44. Am J Respir Cell Mol Biol. 2015 Mar;52(3):342-8 [PMID: 25078322]
  45. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5657-62 [PMID: 10318940]
  46. PLoS One. 2015 Mar 23;10(3):e0118789 [PMID: 25799317]
  47. PLoS One. 2011;6(5):e20077 [PMID: 21625509]
  48. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13588-93 [PMID: 23898208]
  49. J Immunol. 2016 May 15;196(10):4052-63 [PMID: 27076678]
  50. Semin Immunol. 2014 Dec;26(6):431-44 [PMID: 25453224]
  51. J Infect Dis. 1998 Jun;177(6):1563-72 [PMID: 9607834]
  52. Pediatrics. 2009;123(1):e1-8 [PMID: 19367678]
  53. J Clin Neurosci. 2002 Mar;9(2):113-24 [PMID: 11922696]
  54. J Infect Dis. 2005 Dec 15;192(12):2134-41 [PMID: 16288379]
  55. Anal Biochem. 2013 Dec 15;443(2):222-31 [PMID: 24036037]
  56. J Infect Dis. 2012 Feb 15;205(4):586-94 [PMID: 22223854]
  57. Nihon Ronen Igakkai Zasshi. 1997 Oct;34(10):818-24 [PMID: 9455127]
  58. Pediatr Neurosurg. 1998 Aug;29(2):64-8 [PMID: 9792958]
  59. Nature. 2004 Sep 2;431(7004):84-7 [PMID: 15343336]
  60. Acta Neuropathol. 2004 Jul;108(1):17-23 [PMID: 15085359]
  61. Ann Trop Paediatr. 2011;31(4):367-9 [PMID: 22041473]
  62. J Infect Dis. 2005 Dec 15;192(12):2054-8 [PMID: 16288367]
  63. J Neurol Sci. 2000 Dec 1;181(1-2):118-26 [PMID: 11099721]
  64. J Child Neurol. 2006 Apr;21(4):301-8 [PMID: 16900926]
  65. Radiol Clin North Am. 1995 Jul;33(4):733-52 [PMID: 7610242]
  66. Pharmacol Rev. 1997 Jun;49(2):143-55 [PMID: 9228664]
  67. Childs Nerv Syst. 2002 Apr;18(3-4):118-23 [PMID: 11981617]
  68. Clin Infect Dis. 2014 Dec 1;59(11):1638-47 [PMID: 25107295]
  69. Enferm Infecc Microbiol Clin. 2006 Apr;24(4):245-50 [PMID: 16725084]
  70. Neurochem Int. 2004 May;44(6):381-92 [PMID: 14687603]
  71. J Clin Invest. 2016 Mar 1;126(3):1093-108 [PMID: 26901813]
  72. J Immunol. 2003 Mar 15;170(6):3233-42 [PMID: 12626582]
  73. Pediatr Infect Dis J. 2016 Oct;35(10):e301-10 [PMID: 27213261]
  74. Proc R Soc Med. 1949 Mar;42(3):169-74 [PMID: 18126979]
  75. Tuberculosis (Edinb). 2010 Nov;90(6):361-6 [PMID: 20829117]
  76. Infection. 2016 Oct;44(5):633-40 [PMID: 27207494]
  77. FEMS Immunol Med Microbiol. 2009 Dec;57(3):203-13 [PMID: 19732140]
  78. J Infect. 2005 Apr;50(3):193-5 [PMID: 15780412]
  79. Science. 1990 Sep 21;249(4975):1431-3 [PMID: 1698311]
  80. AIDS. 2015 Feb 20;29(4):421-31 [PMID: 25565499]
  81. Lancet Infect Dis. 2007 May;7(5):328-37 [PMID: 17448936]
  82. Trends Cell Biol. 2005 May;15(5):269-76 [PMID: 15866031]
  83. Nat Rev Microbiol. 2009 Feb;7(2):99-109 [PMID: 19148178]
  84. J Exp Med. 1990 Aug 1;172(2):497-507 [PMID: 2373990]
  85. J Infect Dis. 2005 Jul 1;192(1):98-106 [PMID: 15942899]
  86. J Infect Dis. 2017 Apr 1;215(7):1011-1013 [PMID: 28419367]
  87. Indian J Pediatr. 2005 Sep;72(9):755-60 [PMID: 16186677]
  88. Clin Exp Immunol. 2004 Sep;137(3):460-8 [PMID: 15320894]
  89. Am J Respir Crit Care Med. 2013 Nov 1;188(9):1137-46 [PMID: 24047412]
  90. Nat Commun. 2015 Sep 24;6:8451 [PMID: 26399326]
  91. Brain Res. 1991 Feb 1;540(1-2):217-23 [PMID: 2054614]
  92. J Infect Dis. 2006 May 1;193(9):1287-95 [PMID: 16586367]
  93. BMC Infect Dis. 2016 Jun 07;16:251 [PMID: 27267176]
  94. Am J Respir Crit Care Med. 2007 Feb 15;175(4):360-6 [PMID: 17095747]
  95. Br J Pharmacol. 2018 Jan;175(2):192-222 [PMID: 28213892]
  96. Infect Immun. 2000 Jun;68(6):3322-6 [PMID: 10816480]
  97. Infect Immun. 1997 Sep;65(9):3896-905 [PMID: 9284169]
  98. J Infect Dis. 2015 Apr 1;211(7):1154-63 [PMID: 25336729]
  99. FEMS Immunol Med Microbiol. 2003 May 15;36(1-2):63-9 [PMID: 12727367]
  100. QJM. 2018 Jul 1;111(7):455-460 [PMID: 29635544]
  101. Lancet Neurol. 2007 Mar;6(3):230-6 [PMID: 17303529]
  102. Curr Mol Med. 2009 Mar;9(2):94-9 [PMID: 19275620]
  103. BMC Infect Dis. 2016 Oct 18;16(1):573 [PMID: 27756256]
  104. Front Cell Neurosci. 2015 Jun 10;9:212 [PMID: 26113810]
  105. Tuberculosis (Edinb). 2010 Jul;90(4):268-77 [PMID: 20580613]
  106. Infect Immun. 2014 May;82(5):1880-90 [PMID: 24566619]
  107. PLoS One. 2008 Mar 19;3(3):e1772 [PMID: 18350135]
  108. QJM. 1998 Nov;91(11):743-7 [PMID: 10024937]
  109. Infect Immun. 1995 Apr;63(4):1598-602 [PMID: 7534279]
  110. Front Neurosci. 2014 Feb 06;8:12 [PMID: 24567701]
  111. Res Immunol. 1996 Oct-Dec;147(8-9):565-72 [PMID: 9127889]
  112. J Infect Dis. 2010 Feb 15;201(4):553-7 [PMID: 20064071]
  113. J Infect Dis. 2008 Oct 1;198(7):1037-43 [PMID: 18702608]
  114. Antimicrob Agents Chemother. 2002 Jun;46(6):1887-95 [PMID: 12019105]
  115. Cell. 2010 Mar 5;140(5):717-30 [PMID: 20211140]
  116. J Infect Dis. 2006 Oct 15;194(8):1127-1134 [PMID: 16991088]
  117. Clin Infect Dis. 2015 Oct 15;61Suppl 3:S200-16 [PMID: 26409283]
  118. Pediatr Infect Dis J. 1991 Nov;10(11):837-42 [PMID: 1844394]
  119. Clin Immunol Immunopathol. 1997 Aug;84(2):171-6 [PMID: 9245549]
  120. Biochem Biophys Res Commun. 2008 Jul 18;372(1):243-8 [PMID: 18485896]
  121. Nat Rev Neurol. 2016 Aug;12(8):439-54 [PMID: 27364743]
  122. J Infect Dis. 2017 Apr 1;215(7):1029-1039 [PMID: 28419315]
  123. J Child Neurol. 2004 Apr;19(4):250-7 [PMID: 15163089]
  124. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2869-73 [PMID: 16477032]
  125. Indian Pediatr. 1994 Nov;31(11):1345-50 [PMID: 7896331]
  126. Neuroradiology. 2003 Oct;45(10):727-9 [PMID: 14504848]
  127. Biomolecules. 2012 Nov 12;2(4):524-48 [PMID: 24970148]
  128. J Neurol Sci. 2017 Aug 15;379:198-206 [PMID: 28716240]
  129. Ther Adv Neurol Disord. 2013 Nov;6(6):386-97 [PMID: 24228074]
  130. Lancet Infect Dis. 2018 May;18(5):526-535 [PMID: 29395996]
  131. Clin Microbiol Rev. 2008 Apr;21(2):243-61, table of contents [PMID: 18400795]

Grants

  1. 203135/Wellcome Trust
  2. 10218/UK Research and Innovation
  3. 104803/Wellcome Trust
  4. U01 AI115940/NIAID NIH HHS
  5. 10218/Cancer Research UK
  6. MC_U117588499/Medical Research Council
  7. 10218/Wellcome
  8. R01 AI145436/NIAID NIH HHS
  9. /Wellcome Trust

MeSH Term

Central Nervous System
HIV Infections
Humans
Immunity
Mycobacterium tuberculosis
Tuberculosis, Meningeal
Virulence
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 3

Word Cloud

Created with Highcharts 10.0.0cellsTBbraintuberculousmeningitismechanismsprimaryinfectionresponseimmunediseaseTuberculosisremainsleadingcausedeathgloballyDisseminationresultssevereformextrapulmonaryTBMrepresentsmedicalemergencyassociatedhighratesmortalitydisabilityViavariousMycobacteriumtuberculosisMtbbacillusdisseminatessiteovercomesprotectivebarriersenterCNSinducesinflammatoryinvolvingperipheralresidentinitiatescascadepathologicmayeithercontainresultsignificantinjuryreviewstepscerebralfactorscontributevirulenceorganismvulnerabilityhostdiscussclinicalmanifestationsarisingPrioritiesfutureresearchdirectionssuggestedpathogenesisTh17T Lymphocytesendothelialgranulocytesmicrogliamonocytes/macrophagesmycobacterialmyeloidneutrophils

Similar Articles

Cited By